Abnormalities in lipid metabolism occur in patients with all stages of chronic kidney disease (CKD) [1-7]. The most common dyslipidemia in CKD and dialysis is hypertriglyceridemia, whereas the total cholesterol concentration can be high, normal, or low, perhaps due in part to malnutrition . In contrast, the nephrotic syndrome is typically associated with hypercholesterolemia and hypertriglyceridemia.
This topic will review the pathogenesis, epidemiology, and treatment of lipid abnormalities in CKD. The pathogenesis and significance of lipid abnormalities in nephrotic syndrome and following kidney transplantation, the association between CKD and coronary heart disease (CHD), and the management of lipids in patients with CKD who require dialysis, are discussed separately. (See "Lipid abnormalities in nephrotic syndrome" and "Lipid abnormalities after renal transplantation" and "Chronic kidney disease and coronary heart disease" and "Secondary prevention of cardiovascular disease in end-stage renal disease (dialysis)", section on 'Lipid modification'.)
The pathogenesis of most lipid abnormalities in patients with chronic kidney disease (CKD) primary involves defective removal from the circulation. The diminished clearance of triglycerides, which can lead to hypertriglyceridemia, stems both from an alteration in the composition of circulating triglycerides (which become enriched with apolipoprotein C-III) and, perhaps later, from reductions in the activity of lipoprotein lipase and hepatic triglyceride lipase, which are involved in triglyceride removal [3,4,9].
Why lipoprotein lipase activity is reduced in CKD is not well understood, but has been thought to reflect increased inhibitor activity . The associated secondary hyperparathyroidism may play a contributory role, perhaps by increasing calcium accumulation within the cells in the liver and adipose tissue. Studies in humans and experimental animals with CKD suggest that parathyroidectomy can normalize serum triglyceride levels and hepatic lipase activity [10,11]. In experimental animals, benefit can also be achieved with verapamil by a similar mechanism , although this has not been confirmed in humans.
Another possible mechanism for hypertriglyceridemia in CKD is retention of a circulating inhibitor of lipoprotein lipase, such as pre-beta-high density lipoprotein (HDL) . Pre-beta-HDL is a form of apolipoprotein A-I found in the non-lipoprotein fraction of normal plasma.